Parasitic Infection With Toxoplasmosis May Be Linked To Parkinson’s & Alzheimer’s Disease

MedicalResearch.com Interview with:

Under a magnification of 900X, this hematoxylin and eosin-stained (H&E) photomicrograph of a brain tissue specimen revealed a case of neurotoxoplasmosis in a patient who had also been diagnosed with multiple myeloma. Note the Toxoplasma gondii tissue cyst, within which bradyzoites could be seen developing. CDC Image

Rima McLeod, M.D., F.A.C.P, F.I.D.S.A
Professor of Ophthalmology and Visual Sciences,Pediatrics (Infectious Diseases), and The College,
Director, Toxoplasmosis Center,
Senior Fellow,Institute of Genomics, Genetics and Systems Biology, Member, Commitees on Immunology, and Molecular Medicine and Pathogenesis,
Member Global Health Center, Affiliate CHeSS;
Attending Physician, Chicago Medicine,
The University of Chicago

MedicalResearch.com: What is the background for this study?

* One third of humans are infected lifelong with the brain-dwelling, protozoan parasite, Toxoplasma gondii.
* Approximately fifteen million of these have congenital toxoplasmosis.
* The parasite interconverts between slow-growing, encysted bradyzoites and rapid-growing tachyzoites.
* In mice, T. gondii creates a chronic intra-neuronal infection and an inflammatory process.
* Mice with acute and chronic infection have alterations in neurotransmitters, memory, seizures, and neurobehavior.
* Some epidemiologic-serologic studies show associations between seropositivity for T. gondii and human neurologic diseases, for example, Parkinson’s and Alzheimer’s diseases.
* Although neurobehavioral disease is associated with seropositivity, causality is unproven.
* Serologic studies of humans with diverse genetics are not optimal to detect strong associations or directionality.
* Epidemiologic associations also do not reveal parasite-modulated gene networks in human brain that could provide insights into how to cure and prevent resultant diseases.
* We need integrative approaches to examine relationships between brain parasitism and other brain diseases, to provide a foundation to identify key pathways and molecules for drug and vaccine design
* To address these problems, we considered two central questions: (i) If chronic brain parasitism associates with other neurologic diseases, what are they? And (ii) Which macromolecular networks are modulated by the parasite in human brain that lead to neuropathology which could underpin and facilitate design of treatments?
* We hypothesized that a systems approach integrating multiple levels of host parasite interactions might resolve these questions.
* To better understand what this parasite does to human brains, we performed a comprehensive systems analysis of the infected brain.  Continue reading

Diabetes Medication Exenatide Shows Promise In Treating Parkinson’s Disease

MedicalResearch.com Interview with:
Dr Dilan Athauda MRCP
Sobell Department of Motor Neuroscience and Movement Disorders
UCL Institute of Neurology & The National Hospital for Neurology and Neurosurgery
London

MedicalResearch.com: What is the background for this study?

Response: Exenatide is a synthetic version of a naturally occurring protein – exendin-4 – that was originally discovered by Dr John Eng in the early 1990’s in the saliva of the Gila Monster, a venomous lizard native to the Southwestern United states. He and his team were looking for bio-active peptides in insect and lizard venom that could be useful for people with Type 2 diabetes. They discovered that exendin-4 was extremely similar to a human hormone called Glucagon-like peptide-1 (GLP-1).  In humans, GLP-1 is secreted after you eat a meal to stimulate insulin secretion (and inhibit glucagon production) of which the end result is a lowering of blood sugar. Unfortunately human GLP-1 is rapidly broken down by a circulating enzyme called dipeptidyl peptidase IV (DPP-IV) and its effects only last minutes.

Importantly, it was discovered that exendin-4 is naturally resistant to the actions of this enzyme, meaning it’s effects on blood sugar control lasts much longer in the body.  These properties made it very attractive to people trying to treat people with Type 2 diabetes and following many successful randomised controlled trials of patients with Type 2 diabetes in 2005, exenatide was approved for use as a treatment.  During this time, work led by Nigel Greig’s group at the NIA showed that first evidence that exendin-4 had neuroprotective properties, and could protect neurons from a variety of stresses and could also improve growth and rescue degenerating cells. Over the next few years, various groups used exendin-4 in a variety of animal toxin models of Parkinson’s disease and showed that exendin-4 could halt the progression of Parkinsonism and prevent cell death in these models through beneficial effects on inflammation, mitochondrial function and cell survival.

Based on this encouraging pre-clinical data, Professor Foltynie supervised the first small, “open-label”, human trial of exenatide in patients with Parkinson’s disease.  The team found that patients treated with exenatide for 1 year (in addition to their usual medication) had less decline in their motor symptoms when assessed without their medication compared to the control group (just on their usual medication) and this advantage over the control group was still present 1 year after stopping the exenatide injections.  However, this trial was open-label – patients knew they were getting a (potentially beneficial) experimental therapy and so we couldn’t exclude the fact that placebo effects were explaining some of the results we saw.

As a result of the potentially beneficial results seen in this small open label trial we carried out a double-blind, placebo controlled trial.

Continue reading

Extended-Release Amantadine Reduces Dyskinesia in Parkinson’s Disease

MedicalResearch.com Interview with:
Rajesh Pahwa MD
Department of Neurology
University of Kansas Medical Center, Kansas City, KS,

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Dyskinesia are one of the major unmet needs in Parkinson Disease patients. At the present time there are no approved medication for dyskinesia, however immediate release amantadine is used in PD patients with dyskinesia. ADS-5102 is a long acting, extended release capsule formulation of amantadine HCl administered once daily at bedtime. This study investigated the safety, efficacy and tolerability of ADS-5102 in Parkinson’s disease (PD) patients with levodopa-induced dyskinesia.

This was a randomized, double-blind, placebo-controlled study of Parkinson’s disease patients with levodopa-induced dyskinesia. In total, 126 patients were randomized to placebo or 274 mg ADS-5102 administered orally at bedtime. ADS-5102 was associated with a significant reduction in dyskinesia at 12 weeks compared with placebo, as measured by the mean change in Unified Dyskinesia Rating Scale (treatment difference, –7.9; P =.0009). OFF time was significantly reduced in ADS-5102 patients compared to placebo (treatment difference -0.9 hours, p=.017).

Continue reading

Vagotomy May Point To Gut Origin of Parkinson’s Disease

MedicalResearch.com Interview with:

Karin Wirdefeldt, MD, PhD</strong> Associate professor Karolinska Institutet Stockholm, Sweden

Dr. Wirdefeldt

Karin Wirdefeldt, MD, PhD
Associate professor
Karolinska Institutet
Stockholm, Sweden

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: It has been hypothesized that Parkinson’s disease may start in the gut and spread to the brain via the vagal nerve. We found that people who had a truncal vagotomy (ie, the nerve trunk fully resected) at least 5 years earlier were less likely to develop Parkinson’s disease compared to people without vagotomy or people who had a selective vagotomy (ie, only branches of the nerve resected).

Continue reading

Diabetes Drug May Slow Progression of Parkinson’s Disease

MedicalResearch.com Interview with:

Patrik Brundin, M.D., Ph.D. Director, Center for Neurodegenerative Science Van Andel Research Institute

Dr. Patrik Brundin

Patrik Brundin, M.D., Ph.D.
Director, Center for Neurodegenerative Science
Van Andel Research Institute

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The investigational drug at the heart of our study, MSDC-0160, has been in development to treat type 2 diabetes by improving cellular metabolism.

In Parkinson’s, reductions in cellular metabolism slow down vital housekeeping processes that clear out toxic proteins that otherwise accumulate with age. If these proteins aren’t removed, they clump together, leading to the damage and cell death that causes Parkinson’s hallmark symptoms, such as rigidity and tremor. MSDC-0160 helps keep these housekeeping processes working, ultimately protecting the brain.

We demonstrated that MSDC-0160 has strong, reproducible, positive effects across multiple models of Parkinson’s disease—it rescued dopamine-producing cells, improved behavioral deficits in mouse models and reversed inflammation. Overall, we believe it is a strong candidate for repurposing as a potential treatment that actually may slow the disease’s progression, rather than only mitigating symptoms.

Continue reading

Deep Brain Stimulation Improves Parkinson’s Symptoms In Some Patients With SPG 11 Mutations

MedicalResearch.com Interview with:

Adolfo Ramirez Zamora, MD Associate Professor of Neurology and Phyllis E. Dake Endowed Chair in Movement Disorders Department of Neurology Albany Medical College

Dr. Adolfo Ramirez Zamora

Adolfo Ramirez Zamora, MD
Associate Professor of Neurology and
Phyllis E. Dake Endowed Chair in Movement Disorders
Department of Neurology
Albany Medical College

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Patients with SPG 11 mutations can present with motor symptoms characterized by juvenile onset dystonia, Parkinsonism and lower extremity spasticity. Parkinsonism appears to be responsive to levodopa therapy early in the disease but treatment is complicated by the occurrence of motor fluctuations resembling parkinson disease. Patients have short duration of medication effects, unpredictable response to medications along with generalized, excessive involuntary movements known as dyskinesias.

Deep Brain stimulation is a well-established treatment for movement disorders but it has never been used in this disease. We first report the clinical outcome obtained with globus pallidus internal deep brain stimulation in a patient with parkinsonism, dystonia, dyskinesias related to SPG 11. Additionally, we report for the first time the basal ganglia changes observed in the disease using intraoperative neuronal recordings. Patient had a sustained and remarkable response to stimulation over the next two years without side effects. Neurophysiologic changes revealed a unique pattern of neuronal firing despite of the resemblance to advance Parkinsons disease.

Continue reading

Rosa & Co. Develop PhysioMap To Advance Drug Development Programs

MedicalResearch.com Interview with:
Rosa & Co. LLC,Dr. Christina Friedrich
Chief Engineer, PhysioPD
Rosa & Co. LLC

MedicalResearch.com: What is the background for this study?

Response: Elan was developing compounds for the treatment of Parkinson’s Disease. The compounds were designed to modify negative effects of alpha-synuclein on neurotransmitter vesicle trafficking, but these effects are poorly understood. Elan and Rosa collaborated in the development of a Synuclein PhysioMap®, a graphical model architecture to support hypothesis generation and testing. The objectives of the project were to provide insight into alpha-synuclein function in vesicle trafficking, memorialize and communicate the current state of knowledge within Elan, and to recommend experiments to test hypotheses, resolve uncertainties and identify and prioritize potential targets.

Continue reading

Parkinson’s Disease Linked To Increase in Number of Inflammatory Markers

MedicalResearch.com Interview with:

Yong Cheng, PhD, post-doc fellow Section on Cellular Neurobiology Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health Bethesda, Maryland

Dr. Yong Cheng

Yong Cheng, PhD, post-doc fellow
Section on Cellular Neurobiology
Eunice Kennedy Shriver National Institute of Child Health and Human Development
National Institutes of Health
Bethesda, Maryland

MedicalResearch.com: What is the background for this study?

Response: Parkinson’s disease is the second most neurodegenerative disease after Alzheimer’s disease. The symptoms of the disease are typically movement related. However, the nonmotor features in PD are increasingly recognized. Evidence suggests that inflammation may play a role in the development of AD, and a substantial number of studies have demonstrated altered levels of peripheral blood inflammatory cytokines in patients with  Parkinson’s disease, but findings have been inconsistent for individual cytokines and between studies. Therefore, we undertook a systematic review of the scientific literature, using a meta-analysis to quantitatively summarize clinical data on blood cytokine levels in patients with PD, compared with healthy controls.

Continue reading

Promising Study Evaluates Chemotherapy for Parkinson’s and Lewy Body Dementia

MedicalResearch.com Interview with:

Charbel Moussa MD. PhD Assistant Professor of Neurology Director- Laboratory for Dementia and Parkinsonism Clinical Research Director- National Parkinson's Foundation Center for Excellence Translational Neurotherapeutics Program Department of Neurology Georgetown University Medical Center Washington DC.

Dr. Charbel Moussa

Charbel Moussa MD. PhD
Assistant Professor of Neurology
Director- Laboratory for Dementia and Parkinsonism
Clinical Research Director- National Parkinson’s Foundation Center for Excellence
Translational Neurotherapeutics Program
Department of Neurology
Georgetown University Medical Center
Washington DC.

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: We conducted a pilot open label proof-of-concept study to evaluate the safety and tolerability of Nilotinib in participants with advanced Parkinson’s disease (PD) with dementia (PDD) or dementia with Lewy bodies (DLB). Our primary objective is to demonstrate that low oral daily doses of 150mg or 300mg Nilotinib (compared to 600-800mg in cancer) are safe and tolerated.

Our secondary objectives are that Nilotinib will cross the blood brain barier and may inhibit cerebral spinal fluid Abl. Based on preclinical data we also hypothesized that Nilotinib will increase DA levels. Motor and cognitive functions were also measured as exploratory clinical outcomes. Other exploratory outcomes are that Nilotinib may alter PD-related CSF biomarkers DJ-1 and α-synuclein. As most participants in this study had dementia we also explored the effects of Nilotinib on Alzheimer’s Disease-related CSF biomarkers, including Aβ40 and Aβ42, total tau and phosphorylated tau (p-tau).

Continue reading

Single Head Injury Linked To Parkinson’s but Not Alzheimer’s Disease

MedicalResearch.com Interview with:

Paul K. Crane, MD MPH Professor Department of Medicine Adjunct Professor Department of Health Services University of Washington

Dr. Paul Crane

Paul K. Crane, MD MPH Professor
Department of Medicine Adjunct Professor
Department of Health Services
University of Washington

MedicalResearch.com: What is the background for this study?

Response: The background is that the most common experience of head injury with loss of consciousness is an apparent recovery. Sometimes this is very fast, sometimes it takes somewhat longer, but typically people return to their prior baseline. Nevertheless there is concern that the head injury may have set in motion processes that would lead to late life neurodegenerative conditions. Previous research has focused especially on Alzheimer’s disease. A more limited research has focused on Parkinson’s disease.

We used data from three prospective cohort studies that included more than 7,000 people to study the relationship between head injury with loss of consciousness and subsequent risk of Alzheimer’s and Parkinson’s disease. We collected head injury exposure data at study enrollment, at a time when we administered cognitive tests and knew they did not have dementia, so our exposure data are not biased. Each of these studies also performed brain autopsies on people who died, and we evaluated data from more than 1500 autopsies.

Continue reading